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Optimizing periprosthetic fracture management and in-hospital outcome: insights from the PIPPAS multicentric study of 1387 cases in Spain.
No full text20.500.12530/87855The incidence of all periprosthetic fractures (PPF), which require complex surgical treatment associated with high morbidity and mortality, is predicted to increase. The evolving surgical management has created a knowledge gap regarding its impact on immediate outcomes. This study aimed to describe current management strategies for PPF and their repercussions for in-hospital outcomes as well as to evaluate their implications for the community. PIPPAS (Peri-Implant PeriProsthetic Survival Analysis) was a prospective multicentre observational study of 1387 PPF performed during 2021. Descriptive statistics summarized the epidemiology, fracture characteristics, management, and immediate outcomes. A mixed-effects logistic regression model was employed to evaluate potential predictors of in-hospital mortality, complications, discharge status, and weight-bearing restrictions. The study encompassed 32 (2.3%) shoulder, 4 (0.3%) elbow, 751 (54.1%) hip, 590 (42.5%) knee, and 10 (0.7%) ankle PPF. Patients were older (median 84 years, IQR 77-89), frail [median clinical frailty scale (CFS) 5, IQR 3-6], presented at least one comorbidity [median Charlson comorbidity index (CCI) 5, IQR 4-7], were community dwelling (81.8%), and had outdoor ambulation ability (65.6%). Femoral knee PPF were most frequently associated with uncemented femoral components, while femoral hip PPF occurred equally in cemented and uncemented stems. Patients were managed surgically (82%), with co-management (73.9%), through open approaches (85.9%) after almost 4 days (IQR, 51.9-153.6 h), with prosthesis revision performed in 33.8% of femoral hip PPF and 6.5% of femoral knee PPF. For half of the patients, the discharge instructions mandated weight-bearing restrictions. In-hospital mortality rates were 5.2% for all PPF and 6.2% for femoral hip PPF. Frailty, age > 84 years, mild cognitive impairment, CFS > 3, CCI > 3, and non-geriatric involvement were candidate predictors for in-hospital mortality, medical complications, and discharge to a nursing care facility. Management involving revision arthroplasty by experienced surgeons favoured full weight-bearing, while an open surgical approach favoured weight-bearing restrictions. Current arthroplasty fixation check and revision rates deviate from established guidelines, yet full weight-bearing is favoured. A surgical delay of over 100 h and a lack of geriatric co-management were related to in-hospital mortality and medical complications. This study recommends judicious hypoaggressive approaches. Addressing complications and individualizing the surgical strategy can lead to enhanced functional outcomes, alleviating the economic and social burdens upon hospital discharge. Level of Evidence Level IV case series. registered at ClinicalTrials.gov (NCT04663893), protocol ID: PI 20-2041
Consensus on the approach to hydrosaline overload in acute heart failure. SEMI/SEC/S.E.N. recommendations.
No full text20.500.12530/87849Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.)
Violence as a Health Problem.
No full text20.500.12530/87870Violence is a public health problem, and when it affects childhood, it can cause illness throughout the individual's life. Apart from being able to cause damage in the physical, mental and social spheres, it represents a violation of the rights of the affected children, and a high consumption of resources, both economic and social. A multitude of investigations have improved attention to this violence. However, these advances are not consistent with the practical management of victims, both in Primary and Hospital Care. There is a significant area of improvement for paediatric care. Through this article, different professionals from all established paediatric health care facilities develop general lines of knowledge and action regarding violence against children. An overview is taken of the legislation related to childhood, the different types of abuse that exist, their effects, management and prevention. It concludes with an epilogue, through which we aim to move sensibilities. In summary, this work aims to promote the training and awareness of all professionals specialized in children's health, so that they pursue the goal of achieving their patients' greatest potential in life, and in this way, to help create a healthier society, with less disease, and more justice
Unravelling the mechanisms causing murepavadin resistance in Pseudomonas aeruginosa: lipopolysaccharide alterations and its consequences.
No full text20.500.12530/87857Murepavadin is an antimicrobial peptide (AMP) in clinical development that selectively targets Pseudomonas aeruginosa LptD and whose resistance profile remains unknown. We aimed to explore genomic modifications and consequences underlying murepavadin and/or colistin susceptibility. To define genomic mechanisms underlying resistance, we performed two approaches: 1) a genome-wide association study (GWAS) in a P. aeruginosa clinical collection (n=496), considering >0.25 mg/L as tentative cut-off of murepavadin acquired resistance; 2) a paired genomic comparison in a subset of 5 isolates and their isogenic murepavadin-resistant mutants obtained in vitro. Lipid-A composition, immunogenicity and cathelicidin and indolicidin effects on bacterial growth were also tested in this last subset of isolates. Murepavadin MICs were determined in ΔlpxL1 and ΔlpxL2 knock-out mutants obtained from a auxotroph PAO1 derivative. GWAS revealed a missense variant (A→G p.Thr260Ala in the hisJ gene) associated with murepavadin resistance although both resistant and susceptible strains harbored it (21% and 12% respectively, OR=1.92, p=0.012 in χ² test). Among the isolate subset, murepavadin-resistant mutants with deletions in lpxL1 and lpxL2 genes showed lower abundance of hexa-acylated lipid-A (m/z 1616, 1632). 4-aminoarabinose addition was found only in colistin-resistant isolates but not in the other ones, irrespective of murepavadin susceptibility. Accordingly, ΔlpxL1 and ΔlpxL2 mutants exhibited higher murepavadin MICs than parental PAO1 auxotroph strain (2 and 4 vs 0.5 mg/L respectively). Lipopolysaccharide from murepavadin-resistant mutants triggered lower inflammatory responses in human monocytes. Those with lpxL mutations and hexa-acylated lipid-A loss also exhibited greater growth reduction when exposed to host-derived AMPs cathelicidin and indolicidin. High murepavadin-resistance seems to be linked to lpxL1 and lpxL2 mutations and lower hexa-acylated lipid-A, corresponding to lower inflammatory induction and higher susceptibility to host-derived AMPs. Although GWAS identified one variant associated with the murepavadin-resistant phenotype, data revealed that there was no unique single genetic event underlying this phenotype. Our study provides insight into the mechanisms underlying murepavadin susceptibility
Expert perspectives on ECCO2R for acute hypoxemic respiratory failure: consensus of a 2022 European roundtable meeting.
No full text20.500.12530/87908By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4-6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14-15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5-3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14-15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14-15 cmH2O suggested as the primary inclusion criterion
Advancements in Non-Small Cell Lung Cancer Developments in predictive biomarker testing and targeted therapy in advanced stage non-small cell lung cancer and their application across European countries
No full text20.500.12530/87912In the past two decades, the treatment of metastatic non -small cell lung cancer (NSCLC), has undergone significant changes due to the introduction of targeted therapies and immunotherapy. These advancements have led to the need for predictive molecular tests to identify patients eligible for targeted therapy. This review provides an overview of the development and current application of targeted therapies and predictive biomarker testing in European patients with advanced stage NSCLC. Using data from eleven European countries, we conclude that recommendations for predictive testing are incorporated in national guidelines across Europe, although there are differences in their comprehensiveness. Moreover, the availability of recently EMA-approved targeted therapies varies between European countries. Unfortunately, routine assessment of national/regional molecular testing rates is limited. As a result, it remains uncertain which proportion of patients with metastatic NSCLC in Europe receive adequate predictive biomarker testing. Lastly, Molecular Tumor Boards (MTBs) for discussion of molecular test results are widely implemented, but national guidelines for their composition and functioning are lacking. The establishment of MTB guidelines can provide a framework for interpreting rare or complex mutations, facilitating appropriate treatment decision -making, and ensuring quality control. Copyright (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Associations between waist circumference, central obesity, and the presence of non-valvular atrial fibrillation patients with heart failure.
No full text20.500.12530/87857Reportedly, there is a clear correlation between waist circumference (WC) and atrial fibrillation (AF). However, there is no specific discussion about the relationship between WC and non-valvular AF (NVAF) patients with heart failure. Our main purpose was to study the relationship between WC, central obesity (CO), and NVAF patients with heart failure. This is a retrospective cohort study. A total of 3,435 patients with NVAF in the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2017 were enrolled. The targeted independent variable and the dependent variable were WC and CO and the presence of NVAF with heart failure, respectively. Univariate, multiple regression, and subgroup analyses were used to analyze their relationship. We used the receiver operating characteristic (ROC) curve to choose the better predictor of NVAF with heart failure between WC and CO and calculated the proposed cut-off value of WC in males and female separately. The identified risk factors of NVAF with heart failure were sex, height, WC, CO, body mass index (BMI), fasting blood glucose (FBG), homocysteine (HCY), triglyceride (TG), low-density lipoprotein cholesterol (LDLC), hypertension, diabetes mellitus (DM), stroke, vascular disease, and plaque. Then, a binary logistic regression model indicated that the occurrence of NVAF patients with heart failure increased 10% with WC increasing 1 cm and had a 2.8-fold increased risk with CO compared to those without. The predictive value [area under the ROC curve (AUC)], specificity, sensitivity, and accuracy of WC for the disease risk of NVAF with heart failure were higher than those of CO. The proposed cut-off value of WC was 91.85 cm for males and 93.15 cm for females. The diagnostic value of WC for NVAF with heart failure was higher for females than it was for males. Our research found that WC is related to the presence of heart failure in the patients with NYAF and can predict the presence of NVAF with heart failure. Our findings may help to improve the treatment and care strategies of NVAF individuals with abdominal obesity
Levodopa inhalada: de la evidencia a la experiencia.
No full text20.500.12530/87854Most patients with Parkinson's disease experience motor fluctuations or 'off' periods, which impact on their daily activities, increase their disability and diminish their quality of life. They suffer from these fluctuations despite multiple adjustments to the schedules, doses and intake of medication. In this context, on-demand or rescue treatments are necessary to attempt to improve 'off' periods, with drugs that have the pharmacokinetic advantage of a much faster onset of action because their routes of administration are not oral. There are currently three on-demand therapies for the treatment of fluctuations: subcutaneous apomorphine, inhaled levodopa and sublingual apomorphine. Of the three alternatives, subcutaneous apomorphine generally has the fastest onset of action, sublingual apomorphine provides the longest clinical effect, and inhaled levodopa has the most favourable side effect profile. Each of these drugs has its own characteristics: the time before onset of action, the duration of action and different side effect profiles. The choice for each patient will depend on their individual needs and circumstances. To mark the first year of the introduction of inhaled levodopa, we review these therapies, focusing on the experience with this new dosage form of levodopa
Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study.
No full text20.500.12530/87908Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment. This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction. In this multicenter, prospective observational study, data were collected from MS patients who initiated DRF treatment. The study monitored demographic and clinical characteristics, safety outcomes (including adverse events, reasons for discontinuation, and lymphocyte counts), and efficacy outcomes (radiological and clinical activity). A total of 195 MS patients across 26 neurological departments were included, predominantly female (79.5%), with a mean age of 42.17 years, and a mean duration of treatment with DRF of 6.3 months. Most patients (70.3%) reported no adverse events, while gastrointestinal issues and flushing were the most common adverse events observed. The majority of patients (84.6%) continued with DRF treatment, with tolerability issues being the primary reason for discontinuation. Efficacy analysis showed low relapse rates post-DRF initiation, with most patients exhibiting stable or improved Expanded Disability Status Scale scores and radiological assessments demonstrating minimal activity. This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS